This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Globoid cell leukodystrophy, or Krabbe's disease, is a severe disorder of the central and peripheral nervous system caused by the absence of galactocerebrosidase (GALC) activity. We have previously determined that rhesus macaques affected with Krabbe's disease demonstrated marked increases in the levels of expression of iNOS, TNF-alpha, and IL-1 in the affected white matter, colocalizing with globoid cells, activated microglia, and astrocytes. Cytokine mRNA levels revealed markedly increased gene expression of CCL2 in the brain of affected macaques. CCL2-expressing cells were detected throughout the affected white matter, colocalizing with GFAP cells and astrocytes. We are presently performing as complete analysis of cytokine alterations using a Bioplex analysis at various stages of disease progression. Krabbe brain white matter samples are being directly compared to age and sex matched control brain samples from unaffected animals. In addition, we have begun studies to investigate the role of the inflammatory processes on disease progression. We have generated data demonstrating a wave of altered expression of the Toll-like Receptors (TLRs) in the Krabbe brain. The altered expression correlates with the progression of the disease. It is hoped that this analysis will provide an in depth analysis in to the role that the inflammatory process plays in the disease progression and to identify potential targets for therapeutic intervention.